Chiral phosphate anions

Fig. 20 Diastereomeric purity and relative configuration of enantiopure chiral phosphate anions 15 to 18 isolated after initial precipitation...

Unfortunately, in most of the previous examples, the extent of the asymmetry-induction was determined by chiroptical measurements (ORD, CD) that gave qualitative and not quantitative information. The NMR chiral shift efficiency of TRISPHAT 8 and other hexacoordinated phosphate anions was therefore considered as an excellent analytical tool to provide accurate measurement of the induced selectivity by NMR spectroscopy. 

The Z)3-symmetric TRISPHAT anion 88, tris(tetrachlorobenzenediolato)phosphate, is chiral and configurationally stable. It can be resolved by association with chiral ammonium salts such as cinchonidine <1997AGE608, 2004JOC8521>. TRISPHAT 88 displays high selectivity for cinchonidine and does not associate with the related diasteromer cinchonine <1998TL4825>. The selective ion pairing behavior of TRISPHAT has been exploited in... 

Axially chiral phosphoric acid 3 was chosen as a potential catalyst due to its unique characteristics (Fig. 2). (1) The phosphorus atom and its optically active ligand form a seven-membered ring which prevents free rotation around the P-0 bond and therefore fixes the conformation of Brpnsted acid 3. This structural feature cannot be found in analogous carboxylic or sulfonic acids. (2) Phosphate 3 with the appropriate acid ity should activate potential substrates via protonation and hence increase their electrophilicity. Subsequent attack of a nucleophile and related processes could result in the formation of enantioenriched products via steren-chemical communication between the cationic protonated substrate and the chiral phosphate anion. (3) Since the phosphoryl oxygen atom of Brpnsted acid 3 provides an additional Lewis basic site, chiral BINOL phosphate 3 might act as bifunctional catalyst. 

A new catalyst salt (20) that consists of an achiral ammonium ion and a chiral phosphate anion and which catalyses highly enantioselective transfer hydrogenations of ,/J-unsaturated aldehydes to the corresponding saturated derivatives has been developed. The underlying principle, namely asymmetric counteranion-directed catalysis, is claimed to be a new strategy for highly enantioselective synthesis.357... 

Pasquato et al. differentiated enantiomeric thiiranium cations 72 and 73 by H NMR spectroscopy using chiral hexacoordinated phosphate anions <2002TL5517>. Results obtained with BINPHAT 74 were best. Structures of the cations and BINPHAT are shown below. 

The work of Lacour et al. has focused attention on the use of C2-symmetric hexacoordinated phosphate anions for enantio differentiation of chiral cationic dyes and chiral quaternary ammonium cations.Thus the BINPHAT anion (180) whose configuration is controlled by the BINOL ligand, behaves as an efficient NMR shift reagent and chiral inducer of monomethinium dyes (181) as determined by CD and NMR. ... 

Although phosphate monoesters chiral by virtue of oxygen isotope substitutions cannot be used in stereochemical studies of phosphate monoester hydrolysis (since there are only three stable isotopes of oxygen), they have been used profitably in studies of phosphoryl transfer reactions relevant to the question of the intermediacy of monomeric metaphosphate anion in phosphoryl transfer reactions (see Section III,A). The laboratories of Knowles and Lowe have reported general methods for the synthesis of phosphate monoesters chiral by virtue of oxygen isotope substitution, and these syntheses are summarized in this section. 

Mikami and co-workers have reported that axial chirality could be be controlled in gold-bis(phosphanyl)biphenyl (biphep) (213) complexes in a highly stereospecific manner by using the chiral, binaphthol-derived phosphate anion (X ) (200, 214-219), and that the high levels of enantios-electivity could be attained in the intramolecular hydroamination reaction using the enantiopure complexes (Scheme 60). ... 

In the last decades, NMR has evolved as one of the methods used for the determination of chiral species. Among recent examples, chiral hexacoordinated phosphate anion, [bis(tetrachlorobenzenediolato)mono ([l,r]binaphtalenyl-2,2 -diolato)phosphate], (d,i )-BINPHAT (52), as its tetrabutylammonium salt, has found widespread use as a very efficient NMR chiral solvating agent (CSA) for quaternary ammonium cations (quats) derived from a Troger base (53) (Figure 5). ... 

Besides the metal complexes based on Ni and Pd that were previously proved suitable for the asymmetric hydrovinylation reactions, Ru and Co complexes have also been employed in this type of transformation. The one sole example of Ru-catalyzed enantioselective hydrovinylation was reported by the List group in 2012. In their initial studies, they envisioned that Ni complexes with chiral counteranions might enable the desired reaction. However, it was found that these species either were unreactive or did not furnish enantioselective control in the hydrovinylation reactions. In this context, Jiang and List focused their attention on Ru catalysis (Table 9.6). Systematic evaluation on the effects of Ru complexes ligated by different phosphine ligands as well as various chiral phosphate anions introduced by the corresponding silver salts demonstrated that the combination of Ru complex Ru-3 and additive Ag-1 was the optimal catalyst, leading to acceptable results (entry 8). 

The transfer hydrogenation of ketones was subsequently attempted, although for these more challenging substrates chiral primary amines such as L-valine terf-butyl ester were required in order to obtain good yields (68-99%) and enantioselectivities (70-98% ee) [168]. The reaction most likely involves an iminium-phosphate hydrogen bond. Another important application of asymmetric counteranion-directed catalysis developed by the List group is the chiral phosphate anion-directed epoxidation of a, 3-unsamrated carbonyls [169]. 

R179 J. Lacour, Chiral Hexacoordinated Phosphate Anions in Asymmetric Analysis, Synthesis and Catalysis , in Seminars in Organic Synthesis, A. Corbella Summer School, 35 , Gargnano, Italy, June 14-18, 2010, eds. E. Marcantoni and G. Renzi, Societa Chimica Italiana, Rome, Italy, 2010, p. 11. 

A chiral TRIP anion combined with a palladacycle provides an active catalyst for enantioselective rearrangement of allylic imidates to the corresponding amide products (Scheme 98). Although the catalyst contains a chiral palladacycle, the stereoselectivity is induced by the chiral phosphate anion (Scheme 98). 

The same catalyst (93) was applied with success to the first organocatalytic multi component asymmetric Biginelli reaction providing medicinally relevant chiral 3,4-dihydropyrimidini-2-(l//)-ones (94) (Scheme 29)7 Chiral acid-catalyzed inverse electron-demanding aza Diels-Alder reaction of aldimines (95) with electron-rich alkenes (Scheme 30). A new catalyst salt (96) that consist of an achiral ammonium ion and chiral phosphate anion has been developed that catalyzes highly... 

Bringing together the concept of aminocatalysis and the activation mode of chiral phosphoric acids. List and co-workers introduced the concept of asymmetric counter anion directed catalysis (ACDC) and they applied this idea to the asymmetric reduction of enals 47 (Scheme 23) [ 135]. The catalytic species is formed by an achiral ammonium ion 60 and a chiral phosphate anion 59 derived from 3,3 -bis(2,4,6-triisopropylphenyl)-1,1 -binaphthyl-2,2 -diyl hydrogen phosphate 9 (TRIP). 

Scheme 3 Oxocarbenium and iminium ions bound to chiral phosphate anions...

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